The use of cytotoxic products in the treatment of cancer is well known. Equally well known are the difficulties associated with such treatment. Of these difficulties, the lack of cancer-specific cytotoxicity has received considerable attention, albeit with marginal success. Cytotoxic products continue to kill cancer cells and normal cells alike. Such non-specificity results in a number of undesirable side effects for patients undergoing cancer chemotherapy with cytotoxic products including nausea, vomiting, diarrhea, hemorrhagic gastroenteritis, and hepatic and renal damage. Due to normal cell toxicity, the therapeutic dosage of cytotoxic products has been limited such that cancerous cells are not killed to a sufficient level that subsequently prevents or delays new cancerous growth.
The cytotoxic action of toxic lectins, and especially that of ricin and abrin, has been well studied. It is known that toxic lectins consist of two polypeptide chains, A and B, linked by means of disulfide bridge(s). Cytotoxicity is associated with the A chain and its inhibition of protein synthesis in nucleated cells. The B chain is essentially a delivery vehicle for the A chain. The B chain recognizes polysaccharide units at the surface of cells and creates a high affinity interaction with such units. Once the B chain binds with polysaccharide units at the cell surface, the A chain is incorporated into the cell, block ribosomal protein synthesis and untimately leading to cell death.
Toxic lectins of the type of structure and function similar to ricin include abrin, modeccin and mistletoe toxin. One other category of ribosomal inhibiting protein (RIP) is the toxin with only one subunit having functional characteristics analogous to ricin A chain. This type of RIP lacks cytotoxicity to the intact cell because of the inherent absence of a binding fragment analogous to ricin B chain. Examples of RIP's of this latter type include gelonin and pokeweed antiviral protein.